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Subcategories of XY DSD

• Abnormal testis development: dysgenetic testis, testicular agenesis
• Abnormal androgen production: leydig cell aplasia, T-synthesis disorders
• Abnormal androgen receptors: Androgen insensitivity syndromes
• Other: persistent Mullerian duct, vanishing testis, hypogonadotropic hypogonadism

Leydig cell aplasia

• 46 XY + normal female phenotype, but no mullerian structures
• Testes palpable in inguinal canals or labia majora
• Diagnosis: no rise in testosterone after HCG administration, absence of leydig cells on gonadal biopsy

Testosterone biosynthesis disorders

• Congenital lipoid adrenal hyperplasia (StAR deficiency): 46 XY, female/ambiguous genitalia and absent mullerian structures, manage with steroid replacement and gonadectomy
• Cytochrome p450 oxidoreductase (POR) deficiency: ambiguous genitalia, +/- skeletal dysplasia (Antley-Bixler syndrome)
• 3B-HSD deficiency: incomplete masculinization and salt wasting, incomplete virilization, normal wolffian ducts, elevated 3B-HSD, manage with steroid replacement
• 17a-hydroxylase deficiency: undervirilized spectrum with HTN + hypokalemia + salt/water retention, manage with steroid replacement
• 17,20-Lyase deficiency: undervirilization without mullerian structures or salt-wasting
• 17B-HSD oxiodoreductase deficiency: undervirilization with female phenotype at birth, intraabdominal testes and wolffian ducts, puberty causes development of male secondary sexual characteristics, HCG stimulation results in an increased testosterone/androstenedione ratio

Androgen insensitivity syndrome

• All will have 46 XY + normal hormone profile, but spectrum of external genital appearance
• Complete (cAIS): 46 XY, bilateral testes, female external genitalia, absent mullarian structures, decreased axillary/pubic hair, amenorrhea, manage with gonadectomy (postpubertal), hormone replacement
• Gonadal tumors occur in 0.8-2% with cAIS
• Inguinal hernia: 50% with cAIS have inguinal hernias, 1-2% female infants with inguinal hernias have cAIS
• Partial (pAIS): spectrum of ambiguous external genitalia
• Mild (mAIS): male phenotype with potential mild hypospadias, gynecomastia, azoospermia/oligospermia
• Gonad management: previously recommended gonadectomy, now recommend maintaining gonads (can reposition out of inguinal canal) to provide natural T->E production (instead of E supplementation), discuss low but potential cancer risk and can screen annually with US

5a-reductase deficiency

• Neonatal presentation with female to ambiguous genitalia
• Elevated T:DHT ratio, > 20:1 after HCG stimulation
• Gender assignment is individual decision

Persistent Mullerian duct syndrome

• 46 XY and normal male external genitalia...but persistent mullerian structures
• Usually present with one/both undescended testes, bilateral fallopian tubes, uterus, and upper vagina draining into prostatic utricle
• Perform orchiopexy as indicated, removal of structures not necessary